Chondroitin Sulfate and Glucosamine Supplements in Osteoarthritis

The supplements are safe to try, but benefits may be modest.


Chondroitin sulfate and glucosamine are popular supplements used to treat the pain and loss of function associated with osteoarthritis (OA). However, most studies assessing their effectiveness show modest to no improvement compared with placebo in either pain relief or joint damage.

What Is Chondroitin?

Chondroitin is a major component of cartilage that helps it retain water. It is made by the body naturally. For production of supplements, it can be manufactured from the cartilage of animals, like cows, pigs or sharks, or it can be made in the laboratory. The supplement is sold as chondroitin sulfate. In many European countries it is approved as a prescription treatment for OA. In the U.S., it is often combined with a glucosamine supplement.

What Is Glucosamine?

Like chondroitin, glucosamine is a natural compound found in healthy cartilage, particularly in the fluid around the joints. For dietary supplements, it is harvested from shells of shellfish or can be made in the laboratory. It can come in several chemical forms, but the one most used in arthritis is glucosamine sulfate. In laboratory tests, glucosamine showed anti-inflammatory properties and even appeared to help cartilage regeneration.

Chondroitin Sulfate in Osteoarthritis

Chondroitin may provide additional pain relief for some people with knee and hand osteoarthritis. The benefit is usually modest (about 8 to 10 percent improvement) and it works slowly (up to 3 months). Natural Medicines Comprehensive Database (NMCD), which has rated and evaluated more than 80,000 natural drug ingredients and commercial dietary supplements, classified chondroitin as “possibly effective” for knee OA.

A 2011 study published in the journal Arthritis and Rheumatism found chondroitin sulfate to modestly relieve pain and improve function in people with hand OA (the results of this study were not yet taken into account by the NMCD for their recommendation). The supplement was made from fish and taken daily at a dose of 800 mg for 6 months. Patients reported some improvement after 3 months of treatment. A shorter duration of morning stiffness was also noticed. Chondroitin did not improve grip strength. In addition, patients treated with chondroitin did not use less pain medication (acetaminophen) than those taking placebo.

Because no side effects due to chondroitin were reported, it can be tried as an alternative to nonsteroidal anti-inflammatory drugs (NSAIDs) for patients who cannot take NSAIDs and who need long-term treatment. Chondroitin and NSAIDs have not been compared head-to-head; however, other studies of NSAIDs in patients with hand OA showed a similar improvement in hand pain and function as found with chondroitin. The NSAIDs relieve pain more rapidly than chondroitin sulfate, but they may cause more serious side effects (increased risk of gastrointestinal bleeding, heart attack or stroke, and interactions with other medications), particularly in elderly patients.

Glucosamine in Osteoarthritis

Glucosamine may provide modest pain relief for some patients with osteoarthritis of the knee, hip and spine. Natural Medicines Comprehensive Database classified glucosamine as “likely effective” for osteoarthritis, thus rating it higher than chondroitin. Most of the studies included in the recommendation were done in patients with osteoarthritis of the knee. Because glucosamine is very safe, it can be tried in place of NSAIDs in patients who need long-term treatment and cannot take NSAIDs.

However, some studies show that glucosamine provides the same pain relief as a placebo (a pill that does not contain any medicine). This is called a “placebo effect,” in which the patients expect to feel better, so they do. An example is a study published in 2010 in the Journal of the American Medical Association that found glucosamine did not provide additional pain relief compared to placebo in people with chronic lower back pain caused by osteoarthritis in the lower spine. Half of the participants took glucosamine (1,500 milligrams daily) and the other half took a placebo. Both groups said their lower back pain improved by about 50 percent over one year. However, due to small number of people involved in the study, more research is needed to confirm these results for lower spine OA.

Glucosamine and Chondroitin Combination in Osteoarthritis

The most comprehensive long-term study of any supplement—the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)—looked at the combination of chondroitin and glucosamine, both supplements individually, celecoxib (Celebrex) and placebo in patients with knee osteoarthritis.

The first phase of GAIT found that the combination of glucosamine and chondroitin sulfate showed significant relief in a smaller subgroup of study participants with moderate-to-severe knee pain. But there was no effect in the group with mild pain. Those results were published in the New England Journal of Medicine in 2006.

The second phase of the GAIT study published in the journal Arthritis & Rheumatism in 2008 looked at preventing joint damage in the knee. The combination of glucosamine and chondroitin appeared to be no more effective at preventing joint damage caused by osteoarthritis than a placebo. While the differences between the groups were not statistically significant, the participants who lost the least amount of joint space over two years were in the groups taking either glucosamine alone or chondroitin alone. It is possible that taking the two supplements together might limit their absorption into the body, explaining the lower effect of the supplement combination.

In the third phase looking at a total of four years, the supplements in combination or alone had no greater benefit in knee pain relief than celecoxib or placebo. Although the results were not statistically significant, celecoxib achieved the highest odds of attaining at least 20% reduction in pain. These results were published in 2010 in the journal Annals of Rheumatic Disease.

Bottom Line

The American College of Rheumatology in their latest osteoarthritis treatment recommendations published in 2012 does not recommend chondroitin or glucosamine for the initial treatment of osteoarthritis. Chondroitin and glucosamine supplements alone or in combination may not work for everyone with osteoarthritis. However, patients who take these supplements and who have seen improvements with them should not stop taking them. Both supplements are safe to take long-term.

The differences in effectiveness of chondroitin may also be caused by variations in dosing and quality of the supplements. The chondroitin content between different brands can vary a lot. Similar concerns have been raised over glucosamine supplements. Talk with your doctor or pharmacist about which brand to choose when trying out either of these supplements, or a combination product.

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